Contents

Search

histoplasmosis (Ohio Valley fever)

Etiology: - infection caused by Histoplasma capsulatum - largely a disease associated with immunosuppression - HIV1 infection/AIDS - hematologic malignancy Epidemiology: - most common endemic mycosis in U.S. [2] - most likely fungal infection in traveler returning from Central America or South America [15,16] - endemic to Mississipi River Valley, Ohio River Valley, Mexico, Central America & South America - found in soil contaminated with bird or bat droppings - infection is acquired by inhalation of the mold form of the fungus - 4 cases found in Montana 2012-2013 [6]; case in northen Georgia [2] - 19 cases of pulmonary histoplasmosis associated with a family gathering that included a bonfire that burned bamboo from a grove that had been a red-winged blackbird roost [7] - probably underdiagnosed [13] - 1/3 of cases receive antibacterial agents before diagnosis - only 36% undergo fungal-specific tests [13] Pathology: 1) disseminated disease commonly involves the lungs, liver, spleen, lymph nodes, bone marrow, & central nervous system 2) necrotizing granulomatous pneumonitis [15,16] 3) rarely causes cavitary lung lesions [11] 4) eye may be involved [3] Clinical manifestations: 1) most patients asymptomatic - symptom onset 1-3 weeks after exposure - spontaneous recovery in 3 weeks common 2) constitutional symptoms - malaise, weight loss, headache, fever - generally indolent course [11] 3) pulmonary: flu-like syndrome a) non-productive cough, dyspnea, rales b) broncholithiasis c) pulmonary nodules (histoplasmomas) d) reticulonodular infiltrates 4) mediastinitis - granulomatous mediastinitis - fibrosing mediastinitis 5) acute & chronic disseminated disease 6) gastrointestinal a) abdominal cramps b) diarrhea c) melena d) obstruction e) bowel perforation 6) meningitis 8) ulcers on tongue & lips, case with tongue pain [2] 9) pharyngitis - case with associated tonsillar mass [8] 10) lymphadenopathy, hilar adenopathy 11) splenomegaly 12) hepatomegaly Laboratory: 1) complete blood count - anemia, thrombocyotopenina, leukopenia 2) liver function tests - elevated serum transaminases - elevated serum alkaline phosphatase 3) peripheral blood smear may show small yeast forms within neutrophils 4) Histoplasma antigen in tissue/body fluid a) Histoplasma capsulatum Ag in urine (first line) [17] - sensitivity & specificity > 85% in acute & disseminated infection but < 50% in chronic infection [2] b) Histoplasma capsulatum Ag in serum c) Histoplasma capsulatum Ab in CSF 5) culture of organisms from: a) blood b) sputum c) mouth d) bone marrow e) urine f) cerebrospinal fluid (CSF) 6) increasing complement fixation titer 7) serum ferritin may be > 10,000 ug/L [16] 8) serum lactate dehydrogenase generally high [15,16] 9) Histoplasma capsulatum DNA 10) positive skin testing Radiology: - chest X-ray - pneumonitis - scattered nodular opacities or diffuse reticular pattern - pulmonary infiltrates, hilar adenopathy - single round opacity in lower low indistinguishable from blastomycocosis - calcified lesions in later phases of disease - chest CT - diffuse reticulonodular infiltrates [15,16] Differential diagnosis: - blastomycosis - hilar adenopathy & history of exposure to bat or bird dropping distinguish histoplasmosis [2] - yeast forms of blastomycosis have a distinct appearance with broad-based budding - coccidioidomycosis - chest imaging: focal opacity, thin walled, apical cavities - paracoccidioidomycosis - asymptomatic primary pulmonary infection, acute disseminated infection <10% - Listeria monocytogenes* - tuberculosis - sarcoidosis: pancytopenia not common - malignancy - methotrexate toxicity: no lymphadenopathy * both histoplasmosis & listeriosis associated with immunodeficiency due to TNF-alpha inhibitors [15] * Listeria monocytogenes more likely to cause diarrhea [15] Management: 1) mild forms may not require antifungal therapy (even with pulmonary infiltrates & hilar adenopathy) [2] - most patients recover spontaneosly within 3 weeks 2) itraconazole a) 200 mg TID for 3 days, then - 200 mg PO BID for 6-12 weeks (mild-moderate infection) - 200 mg PO QD for lifelong suppression (98% effective) 3) liposomal amphotericin B followed by itraconazole for severe infection - disseminated infection, immunocompromised, mechanical ventilation - conventional amphotericin B 0.5-0.6 mg/kg/day for several weeks is alternative [2] 4) fluconazole is less effective than itraconazole - up to 800 mg/day is required for 74% suppression

Related

Histoplasma capsulatum histoplasmin (Histolyn-CYL)

General

mycosis; fungal infection

References

  1. DeGowin & DeGowin's Diagnostic Examination, 6th edition, RL DeGowin (ed), McGraw Hill, NY 1994, pg 895
  2. Medical Knowledge Self Assessment Program (MKSAP) 11, 15, 16, 17, 18, 19. American College of Physicians, Philadelphia 1998, 2009, 2012, 2015, 2018, 2021. - Medical Knowledge Self Assessment Program (MKSAP) 19 Board Basics. An Enhancement to MKSAP19. American College of Physicians, Philadelphia 2022
  3. Dylewski J. Acute pulmonary histoplasmosis. CMAJ. 2011 Oct 4;183(14):E1090. PMID: 21810958
  4. Wheat LJ, Freifeld AG, Kleiman MB Clinical practice guidelines for the management of patients with histoplasmosis: 2007 update by the Infectious Diseases Society of America. Clin Infect Dis. 2007 Oct 1;45(7):807-25 PMID: 17806045
  5. Kauffman CA. Histoplasmosis. Clin Chest Med. 2009 Jun;30(2):217-25, PMID: 19375629
  6. Haselow DT et al Centers for Disease Control and Prevention (CDC) Histoplasmosis in a State Where It Is Not Known to Be Endemic - Montana, 2012-2013 MMWR, October 25, 2013 / 62(42);834-837 http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6242a2.htm
  7. Centers for Disease Control and Prevention (CDC) Histoplasmosis Associated with a Bamboo Bonfire - Arkansas, October 2011. MMWR Weekly
  8. Durand ML et al Case 32-2014 - A 78-Year-Old Woman with Chronic Sore Throat and a Tonsillar Mass. N Engl J Med 2014; 371:1535-1543. October 16, 2014. PMID: 25317874 http://www.nejm.org/doi/full/10.1056/NEJMcpc1406191
  9. McKinsey DS, McKinsey JP. Pulmonary histoplasmosis. Semin Respir Crit Care Med. 2011 Dec;32(6):735-44. Review. PMID: 22167401
  10. Knox KS, Hage CA. Histoplasmosis. Proc Am Thorac Soc. 2010 May;7(3):169-72. Review. PMID: 20463244
  11. NEJM. Knowledge+ Question of the Week. July 11, 2017 https://knowledgeplus.nejm.org/question-of-week/319/answer/E/?utm_source=pfw&utm_medium=email&utm_campaign=qoweng
  12. Hage CA, Azar MM, Bahr N, Loyd J, Wheat LJ. Histoplasmosis: Up-to-Date Evidence-Based Approach to Diagnosis and Management. Semin Respir Crit Care Med. 2015 Oct;36(5):729-45. PMID: 26398539
  13. Benedict K, Beer KD, Jackson BR. Histoplasmosis-related healthcare use, diagnosis, and treatment in a commercially insured population, United States. Clin Infect Dis 2019 Apr 30; PMID: 31037290 https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciz324/5481778
  14. Wheat LJ, Azar MM, Bahr NC, Spec A, Relich RF, Hage C. Histoplasmosis. Infect Dis Clin North Am. 2016 Mar;30(1):207-27 PMID: 26897068 Review
  15. NEJM Knowledge+ Allergy/Immunology
  16. NEJM Knowledge+ Complex Medical Care - Vergidis P, Avery RK, Wheat LJ et al Histoplasmosis complicating tumor necrosis factor-alpha blocker therapy: a retrospective analysis of 98 cases. Clin Infect Dis. 2015 Aug 1;61(3):409-17 PMID: 25870331 PMCID: PMC4796723 Free PMC article
  17. Smith DJ, Free RJ, Thompson Iii GR et al. Clinical testing guidance for coccidioidomycosis, histoplasmosis, and blastomycosis in patients with community-acquired pneumonia for primary and urgent care providers. Clin Infect Dis 2023 Oct 6; [e-pub]. PMID: 37802909 https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciad619/7295325
  18. National Eye Institute: Ocular Histoplasmosis http://www.nei.nih.gov/health/histoplasmosis/index.asp